POS0071 THE EFFICACY OF PIRFENIDONE COMBINED WITH IMMUNOSUPPRESSANT THERAPY IN THE CONNECTIVE TISSUE DISEASE-ASSOCIATED PULMONARY INTERSTITIAL DISEASE, A 24-WEEK PROSPECTIVE CONTROLLED COHORT STUDY
Authors: J. Wang, X. Wang, X. Qi, Y. Cui, T. Zhang, Q. Shu
Journal: Annals of the Rheumatic Diseases (2022)

Background Pulmonary interstitial disease(ILD)is very common in connective tissue disease (CTD). Different subtypes display significant differentiations in prognosis. Pirfenidone (PFD), the targeted anti-fibrosis and anti-inflammatory drug, started to apply in CTD-ILD, while its strategy of combination with immunotherapy, bridging time and service time are worth discussing. Objectives To evaluate the efficacy and safety of PFD combined with immunosuppressant (IS) in the treatment of several CTD- ILD. Methods 111 CTD-ILD patients were involved from Aug 2019 to Dec 2021 (ClinicalTrials.gov Identifier NCT04928586 ), including systemic sclerosis (SSc, n=30), inflammatory myopathy (IIM, n=51), rheumatoid arthritis (RA, n=17) and other CTDs (such as systemic lupus erythematosus, sjogren’s syndrome, n=13). Patients were treated with relative stable dose of glucocorticoid (GC) and/or IS since screening.After the evaluation of HRCT, pulmonary function (FVC% and DLCo%) and basic disease activity, PFD was added or not and followed up regularly for 24 weeks. The changes of lung function and imaging were recorded in different subgroups. Results At baseline, The FVC% in the SSc-PFD (n=14), IIM-PFD (n=25) pts were lower than that of SSc-no-PFD (n=16), IIM-no-PFD (n=26) respectively, that was 81.06 vs 99.63( p = 0.014), 78.23 vs 91.12, ( p = 0.010). And IIM-PFD group present a lower baseline DLCo% than IIM-no-PFD pts (64.25 vs 72.82, p =0.034). DLCo% in the other CTDs was lower than SSc, IIM, RA pts (54.58 vs 65.55, 68.71, 66.89, p =0.036), while there were no significant differences in baseline FVC% among these disease. After 24 weeks of treatment, FVC% in SSc-PFD group was improved by 7.15%, while that was -0.91% in SSc-no-PFD pts ( p =0.042). The elevation in FVC% was also significant between the IIM-PFD and IIM-no-PFD control (8.00 vs 1.40, p =0.016). On the other hand, DLCo% of RA-PFD obviously enhanced 7.40%, compared with RA-no-PFD decrease 5.50% from baseline( p =0.002) (Figure 1). Figure 1. The changes of FVC% and DLco% in PFD treated CTD-ILD for 24 weeks. (A ) FVC% changes in SSc, IIM, RA and other CTD-ILD from baseline.; (B ) DLco% changes in SSc, IIM, RA and other CTD-ILD from baseline. * p &lt; 0.05, compared to no PFD treatment group. When performing subgroup analysis with manifestations in HRCT, the change of FVC% in SSc-PFD pts with usual interstitial pueumonia tendency(SSc-PFD-UIP) was higher than SSc-PFD-non-UIP group (8.05 vs -3.20, p =0.014). However, the non-UIP tendency in IIM-PDF pts displayed superior therapeutic effects than IIM-PDF-UIP pts (10.50 vs 1.00, p =0.005). In addition, DLCo% improved significantly in RA-PDF-non-UIP subgroup, compared with RA-PDF-UIP pts (10.40 vs -4.45, p =0.017). According to whether the baseline FVC% and DLCo% value was less than 70%, the improvement of FVC% was significantly higher in PFD treatment group than no-PFD pts of SSc and IIM with baseline High-FVC%(6.60 vs 0.10, p =0.047),(6.30 vs 1.10, p = 0.089).In RA-PFD pts, DLCo% showed a significant increase in baseline DLCo% less than 70% subgroup, compared to RA-no-PDF (7.40% vs -6.60%, p=0.011).The basic IS were considerable between PFD andno-PFD pts throughout the study and no differences of GS and IS dosages at baseline and follow up among all subgroups. Multiple linear regression analysis found that baseline FVC%&lt;70%(HR=4.56,6.81) and prescription of PFD(HR=4.56,4.37) could positively affect the changes of FVC% and DLCo% (all p &lt;0.05). Conclusion The response of pulmonary function to PFD were varied in different CTD-ILD subsets. SSc and IIM pts acquired obviously improvement on FVC%, especially with high baseline FVC group. DLco% elevated in RA-PFD, highlight those baseline Low-DLco and No-UIP pts. Acknowledgements Funded by ECCM Program of Clinical Research Center of Shandong University (No. 2021SDUCRCB010) Disclosure of Interests None declared